中药“五味”现代科学内涵的诠释—中药“苦味”与胃肠道苦味受体的相关性和关联机制研究

Five flavors of TCM is the important part and core content of herbs property theory. Constrained by history, the scientific connotation and mechanism is in the innocent state, because of confusion between natural property(five taste) and functional property(five flavors). And obviously, it is not beneficial for further improvement of herbs property theory and long-term development of TCM. Long being engaged in scientific connotation research about herbs property theory, we realize that there is more important physiological and pathological meaning of taste receptors in gastrointestinal tract than that in oral cavity, when studying the interactive relationship among taste receptors in alimentary tract and five flavors of TCM. In preliminary study, we’ve found some new research clue that expression of gastrointestinal bitter taste receptors (BTRs) can be regularly up-regulated by several ingredient of bitter TCM. And it help us put forward new project for further investigation: gastrointestinal BTRs maybe the common bioeffect link and target of bitter TCM. Thus based on the process such as expression of gene/protein of BTRs, its function, signal transmission and secretion, we plan to reveal the connotation and molecular biological mechanism of bitter flavor of TCM at different levels of cell in vitro, organ in vitro and animal in vivo. We expect it can provide some modern theory basis and standard for scientific definition of bitter flavor of TCM.

中药“五味”是中药药性理论体系的重要组成部分和核心内容。囿于历史年代，中药五味的自然属性（滋味五味）和功能属性（理论五味）混淆不清，其现代生物内涵和机制基本处于“无知”状态，显然不利于中药药性理论体系的进一步完善和中医药的长远发展。我们课题组长期从事中药药性理论的现代诠释研究，在探索口腔味觉受体和胃肠道味觉受体与中药五味契合关系研究中认识到，相比于口腔味觉受体的感受功能，胃肠道味觉受体具有更为重要的生理和病理意义，并在前期工作中发现了新的科研线索—源于多种苦味中药的成分能够规律性地上调胃肠道苦味受体，为我们提出了值得深入研究的新课题—胃肠道苦味受体可能是苦味中药共性的生物效应环节和作用靶点。基于此，本项目拟在细胞、离体器官、整体动物三个层面，基于胃肠道苦味受体基因蛋白表达和受体功能、受体后转导信号以及内分泌效应环节，揭示苦味内涵和生物分子机制，为中药苦味的科学界定提供现代理论依据和标准。

中药五味属性是中药药性理论中的核心药性之一。由于中药中个药的五味属性部分来源于临床功效的观察，部分属于真实滋味，还有的是由五行推演出来的，限制了中药五味在中医临床过程的指导作用，另一方面中药五味属性的药效机理和化学物质基础尚不十分明确，也阻碍了药性理论的标准化和客观化进程。苦味中药是五味属性中的一大类，与中药的功效关系密切。本研究中，我们选择了临床常用、药效确切的苦味中药（黄连、黄芩、黄柏、苦参等）以及主要活性成分，基于苦味受体通路，展开了体内体外的试验研究。研究结果表明，苦味中药能够上调相应苦味受体的基因和蛋白表达，进而提高受体后活性物质的分泌等功能；而对TRPM5等未见显著性影响。鉴于种属差异，有关动物的研究发现我们在人源的小肠细胞株HuTu80上进一步进行了实验验证，选取了受试成分中，黄连素和大黄素分别能够上调T2R38和T2R9的表达，进一步提示，苦味中药黄连和大黄入体后发挥药理作用的分子机制可能与所含的活性成分调节相应苦味受体的表达相关。五味属性是药性理论体系的重要组成部分和核心内容，该研究提供了一种中药五味属性的研究模式，该研究结果和结论为全面解析中药五味属性的现代科学内涵积累了有效数据。